Anti-PD-1 therapy has been clinically effective against a wide range of cancers, but still only a fraction of patients achieve a durable response. Researchers have been on the hunt for biomarkers that could predict which patients are likely to respond to this therapy, and Krieg et al. may have finally found their mark. The team utilized peripheral blood mononuclear cells (PBMCs) from samples from twenty patients with metastatic melanoma before and twelve weeks after the initiation anti-PD-1 immunotherapy to compare responders and non-responders. They used high-dimensional, single-cell mass cytometry with three optimized immune marker panels and several bioinformatics tools to identify differences between responders and non-responders to anti-PD-1 immunotherapy.
Since the beginning of my scientific career, reaching back to my graduate studies, I was always interested in combining cell biology with conventional flow cytometry, and I followed the rapid development of the flow cytometry field as it went from being able to monitor four parameters all the way up to 16 parameters. In 2014, as an independent fellow with a focus on translational immunology in the University Research Priority Program (URPP) in Zurich, Switzerland and while still deciding on whether to pursue a career in academic science or industry, I had the opportunity to join the laboratory of Burkhard Becher. At that time Burkhard was returning from a sabbatical in the laboratory of Evan Newell at the A*Star Institute, Singapore, where he got insights into the new technology of mass cytometry (MC). MC uses rare metal-labeled probes instead of the more common fluorochrome-labeled probes, thus avoiding spectral overlap from conventional flow, tissue auto-fluorescence and being able to potentially detect up to 100 markers per cell (although, due to practical restrictions, about 50 markers are more realistic to date).